The hypothesis being tested in this project is the alterations in circulating gastrointestinal hormones are instrumental in regulating the rate of gastric acid secretion under normal and pathological conditions. We are examining the release and biological activity of the various molecular forms of gastrin in normal subjects and in patients with peptic ulcer disease. We have found that hepatadecapeptide gastrin (G-17) is the most potent circulating gastrin and are attempting to determine the contribution of G-17 to acid secretion stimulated by an amino acid meal. In addition we will determine whether inhibition of G-17 release at low intragastric pH is abnormal in duodenal ulcer patients. Recently we identified a circulating substance, distinct from gastrin, in patients with gastric hypersecretion. We will characterize this substance.